The Pathogenic Role of Persistent Milk Signaling in mTORC1- and Milk- MicroRNA-Driven Type 2 Diabetes Mellitus

DC FieldValueLanguage
dc.contributor.authorMelnik, Bodo C.
dc.date.accessioned2021-12-23T15:57:54Z-
dc.date.available2021-12-23T15:57:54Z-
dc.date.issued2015
dc.identifier.issn15733998
dc.identifier.urihttps://osnascholar.ub.uni-osnabrueck.de/handle/unios/3203-
dc.description.abstractMilk, the secretory product of the lactation genome, promotes growth of the newborn mammal. Milk delivers insulinotropic amino acids, thus maintains a molecular crosstalk with the pancreatic beta-cell of the milk recipient. Homeostasis of beta-cells and insulin production depend on the appropriate magnitude of mTORC1 signaling. mTORC1 is activated by branched-chain amino acids (BCAAs), glutamine, and palmitic acid, abundant nutrient signals of cow's milk. Furthermore, milk delivers bioactive exosomal microRNAs. After milk consumption, bovine microRNA-29b, a member of the diabetogenic microRNA-29-family, reaches the systemic circulation and the cells of the milk consumer. MicroRNA-29b downregulates branched-chain alpha-ketoacid dehydrogenase, a potential explanation for increased BCAA serum levels, the metabolic signature of insulin resistance and type 2 diabetes mellitus (T2DM). In non-obese diabetic mice, microRNA-29b downregulates the antiapoptotic protein Mcl-1, which leads to early beta-cell death. In all mammals except Neolithic humans, milk-driven mTORC1 signaling is physiologically restricted to the postnatal period. In contrast, chronic hyperactivated mTORC1 signaling has been associated with the development of age-related diseases of civilization including T2DM. Notably, chronic hyperactivation of mTORC1 enhances endoplasmic reticulum stress that promotes apoptosis. In fact, hyperactivated beta-cell mTORC1 signaling induced early beta-cell apoptosis in a mouse model. The EPIC-InterAct Study demonstrated an association between milk consumption and T2DM in France, Italy, United Kingdom, Germany, and Sweden. In contrast, fermented milk products and cheese exhibit an inverse correlation. Since the early 1950's, refrigeration technology allowed widespread consumption of fresh pasteurized milk, which facilitates daily intake of bioactive bovine microRNAs. Persistent uptake of cow's milk-derived microRNAs apparently transfers an overlooked epigenetic diabetogenic program that should not reach the human food chain.
dc.language.isoen
dc.publisherBENTHAM SCIENCE PUBL LTD
dc.relation.ispartofCURRENT DIABETES REVIEWS
dc.subjectALPHA-KETOACID DEHYDROGENASE
dc.subjectbeta-cell apoptosis
dc.subjectBranched-chain amino acid dysmetabolism
dc.subjectCHAIN AMINO-ACIDS
dc.subjectDAIRY CONSUMPTION
dc.subjectdiabetogenic milk-derived microRNAs
dc.subjectDIET-INDUCED OBESITY
dc.subjectEndocrinology & Metabolism
dc.subjectendoplasmic reticulum stress
dc.subjectENDOPLASMIC-RETICULUM STRESS
dc.subjectGROWTH-FACTOR-I
dc.subjectIMMUNE-RELATED MICRORNAS
dc.subjectINSULIN-RESISTANCE SYNDROME
dc.subjectMAMMALIAN TARGET
dc.subjectMESENCHYMAL STEM-CELLS
dc.subjectmTORC1
dc.subjecttype 2 diabetes mellitus
dc.titleThe Pathogenic Role of Persistent Milk Signaling in mTORC1- and Milk- MicroRNA-Driven Type 2 Diabetes Mellitus
dc.typejournal article
dc.identifier.doi10.2174/1573399811666150114100653
dc.identifier.isiISI:000374286900006
dc.description.volume11
dc.description.issue1
dc.description.startpage46
dc.description.endpage62
dc.identifier.eissn18756417
dc.publisher.placeEXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES
dcterms.isPartOf.abbreviationCurr. Diabetes Reviews
dcterms.oaStatusGreen Published, Green Submitted
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